Adsorbents are widely used in medical technology. Adsorbers with adsorbents which remove low-density lipoproteins (LDL) from blood or blood constituents or reduce the concentrate thereof, such as those known from German Patent No. 39 32 971 (‘DE '971’) are known. DE '971 describes an adsorbent material as an organic carrier with a fixed particle size and an exclusion limit, carrying a functionality at its surface to which the LDL molecule binds.
There are LDL adsorbers made of porous polymethacrylate particles coated with polyacrylic acid (PAA), where PAA is present in bound form on the outer surface bordering the particles as well as on the inner surface enclosing the pores. Since blood cells have only minor interactions with PAA, such an adsorbent is suitable for whole blood, e.g., the adsorbent particles allow blood cells to pass through without interacting with them, e.g., without activating, binding or damaging them. Thus, according to this method all the blood may be passed through the adsorber without prior separation of the blood cells. The LDL is separated out here through a size exclusion mechanism and not by way of a specific binding of LDL to a functional group adhering to the carrier.
It is not typical for an adsorbent to be compatible with whole blood, because the carrier material normally leads to complement activation and/or triggers platelet aggregation and adhesion.
Whole blood compatibility depends in particular on the coating used with functional groups. When using certain functional groups known in the related art, it is impossible to produce adsorbers that are compatible with whole blood because they interact with the blood cells. One example of this is an adsorber for binding immune complexes, where the adsorber carries the protein Clq as a functional group on its surface. The protein enters into an interaction with immunoglobulins and may remove them from their solutions. However, blood cells, in particular platelets, also have a binding site with the protein C1q, and they are also bound to such adsorbents. Thus, whole blood cannot pass through these adsorbents unimpaired. The same problems also occur with so-called fibrinogen absorbers.
In such cases, the blood cells are first separated from the blood plasma, whereupon only the plasma is passed through the adsorber. After separation of the immune complexes by binding to the Clq protein, the blood cells are combined again with the purified blood plasma. This procedure is complicated and is a burden for the patient as well as being a high-risk procedure.
The whole blood adsorbents described in the literature (e.g., Dräger et al., Eur. J. Clin. Invest. 1998, 28 (12); U.S. Pat. No. 5,476,715 A) consist of particles so large that they form interspaces in which the blood cells can move. Furthermore, the particles have pores leading to an internal surface. These pores are large enough that even macromolecules can penetrate into them. However, these pores are so small that blood cells are prevented from penetrating into them. Thus, blood cells come in contact only with the outer surface of the particles. Furthermore, according to European Patent No. 0 424 698, these particles must be as spherical and unaggregated as possible to have a “smooth” and inert outside, so that the platelets will slide past them.
German Patent Application 198 42 785 A1 describes porous materials whose surfaces are chemically functionalized so that the outer surface of the porous materials is electroneutral and hydrophilic, while the inner surface may even be provided with so-called functional ligands. Materials compatible with whole blood are not described there, however. These porous materials are produced by first introducing epoxy groups into a porous base carrier, whereby both the pore surfaces and the outer surface of the base carrier are functionalized with epoxy groups, and then the epoxy groups are catalytically opened by reaction with a nucleophile. In this process, a particulate catalyst having a particle size larger than the average pore diameter of the porous base carrier is used, so that no reaction can take place in the pores. Then the remaining epoxy groups at the pore surfaces are converted by introducing functional ligands. However, using a particulate catalyst entails some considerable disadvantages, because it is difficult to separate the particulate catalyst from the coated carrier material. Furthermore, a reaction may and can take place only at the points of contact between the catalyst particles and the carrier material particles, so that very long reaction times and extensive stirring are necessary to achieve an approximately complete reaction at the surface. Furthermore, prolonged stirring can result in abrasion of the catalyst particles, so the adsorber may become contaminated with catalyst residues. Furthermore, when magnetic catalyst particles are used, the possibility of catalyst particles remaining in the adsorbent cannot be ruled out. However, these catalyst particles may lead to problems, especially in purifying whole blood, due to interactions with the constituents of blood, so that such a catalyst is not compatible with whole blood.
Thus, one object of the present invention is to provide an adsorbent which is compatible with whole blood and carries groups in locations that are not accessible to blood cells, these groups being capable of interacting with substances to be separated from the blood. Furthermore, another object of the present invention is to provide a method with which such an adsorbent can be produced easily and economically.